Bragg William, Norton Dean, Shamsi Shahab A
Department of Chemistry, Center of Biotechnology and Drug Design, Georgia State University, Atlanta, GA 30303, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Nov 1;875(1):304-16. doi: 10.1016/j.jchromb.2008.06.028.
This work focuses on the simultaneous analysis of beta-blockers with multiple stereogenic centers using capillary electrochromatography-mass spectrometry (CEC-MS) with a vancomycin stationary phase. The critical mobile phase variables (composition of organic solvents, acid/base ratios) as well as column temperature and electric field strength, effecting enantioresolution and analysis time were first optimized sequentially. Next, to achieve global optimum a multivariate D-optimal design was used. Although multivariate approach did not improve enantioresolution any further, analysis time was significantly reduced. Under optimum CEC-MS conditions, all stereoisomers were resolved with resolution in the range 1.0-3.1 in less than 60 min with an average signal-to-noise (S/N) greater than 1000. The developed CEC-MS method has the potential to emerge as a screening method for analysis of multiple chiral compounds using a single protocol using the same column and mobile phase conditions, thus reducing the operation time and cost.
本研究聚焦于使用具有万古霉素固定相的毛细管电色谱-质谱联用（CEC-MS）技术同时分析具有多个手性中心的β-受体阻滞剂。首先依次优化了影响对映体拆分和分析时间的关键流动相变量（有机溶剂组成、酸碱比例）以及柱温和电场强度。接下来，为实现全局最优，采用了多变量D-最优设计。尽管多变量方法并未进一步提高对映体拆分度，但分析时间显著缩短。在最优的CEC-MS条件下，所有立体异构体在不到60分钟内实现了1.0至3.1的拆分度，平均信噪比（S/N）大于1000。所开发的CEC-MS方法有潜力成为一种筛选方法，可使用相同的色谱柱和流动相条件，通过单一方案分析多种手性化合物，从而减少操作时间和成本。
